The present invention relates generally to medical devices and, more particularly, to a radioactive medical device having beta radiation emitting capabilities for inhibiting an undesired hyperplastic response to the healing of biological tissue, and a method for making and using the devices.
In patients with arterial occlusive disease, vascular surgeons use sutures to anastomose autogenous vein, prosthetic grafts, or arteries to other arteries in order to bypass around or replace diseased arterial segments. At virtually all anastomotic sites between the arteries and autogenous vein, or prosthetic grafts, a condition of rapid cellular growth termed xe2x80x9cintimal hyperplasiaxe2x80x9d may occur.
Intimal hyperplasia is the usual response to blood vessel injury. This rapid cellular growth, as a response to injury of the blood vessel cellular lining, begins to narrow the opening between the vessels and/or graft to the point where an occlusion may occur. More specifically, intimal hyperplasia forms as a result of smooth muscle cell proliferation, migration, and extracellular matrix deposition. The interaction of platelets, macrophages, growth factors, and cytokines plays an important role in the process. Intimal hyperplasia is the primary cause of xe2x80x9crestenosisxe2x80x9d (narrowing) in the first year after vascular bypass operations and may cause indwelling venous catheters to occlude as well. Usually, the patient must have another operation to revise or replace the occluded graft. If a major vein occludes (e.g. jugular or subclavian) massive edema of the upper extremity, face and neck may occur and if an artery occludes, it could possibly lead to potential limb loss.
Of course, intimal hyperplasia is merely a subset of a larger problem involving hyperplasia resulting from smooth muscle cell proliferation, migration, and extracellular matrix deposition. In general, when biological tissue begins grafting, or healing, an undesirable hyperplastic response may occur. It would be desirable to limit, or even prevent such an unwanted hyperplastic response.
The most frequently performed prosthetic graft operation is an arterial to venous conduit for dialysis in chronic renal failure patients. Renal dialysis patients require repetitive angioaccess to this arterialxe2x80x94venous graft for dialysis to rid their system of toxins. The most commonly used graft for dialysis is a synthetic graft made from teflon or ePTFE (expanded polytetrafluroethylene). Unfortunately, these grafts rapidly fail and have a primary occlusion rate of 15% to 50% during the first year, with a mean patency of only 15 months. This failure in most cases is due to the development of intimal hyperplasia at the venous anastomosis. Again, there is a strong desire in the art to prevent this unwanted hyperplastic response.
Both of the examples of tissue grafting outlined above, surgery as a result of arterial occlusive disease and an arterial to venous conduit for dialysis, prescribe the use of a suture to assist the healing of biological tissue. However, there are several devices currently used in the medical field for assisting the grafting of biological tissue. For example, sutures, xe2x80x9cpatchesxe2x80x9d and meshes are used to hold tissues in place and give the tissues time to heal. Similarly, stents come in a variety of configurations for supporting blood vessel walls in an attempt to inhibit stenosis of the vessel.
Surgical sutures are used to bring together ends of biological tissue and hold them in place until the joining tissues have time to heal. As another example, in some types of medical operations, medical personnel may use xe2x80x9cpatchesxe2x80x9d or meshes to hold damaged tissue in order to give the tissue appropriate time to heal. These xe2x80x9cpatchesxe2x80x9d function in a manner similar to sutures, but are much quicker to apply and may be effective where a suture would not be appropriate. Just as with vascular bypass operations and the restenosis that may occur, the tissue held by the xe2x80x9cpatchxe2x80x9d or mesh may also exhibit signs of hyperplasia that are undesirable, if not harmful.
In recent years, studies have been conducted in animal models whose vessels have undergone angioplasty. It was found that the vessels response to injury from balloon angioplasty is similar to that observed at suture anastomotic lesions. Studies conducted at Emory University, Atlanta, Ga., U.S.A., and Vanderbilt University, Nashville, Tenn., U.S.A., suggest that restenosis results primarily from the migration and rapid proliferation of a smooth muscle type cell after balloon angioplasty. It has been demonstrated by these groups that very low levels of beta-particle irradiation introduced to the site of injury following angioplasty markedly inhibits smooth muscle cell proliferation and or migration. Numerous other studies have been conducted which have demonstrated and substantiated these early findings.
U.S. Pat. No. 5,897,573, filed Apr. 22, 1997, dealt with the problem of unwanted hyperplastic response in biological tissue by suggesting the irradiation of a suture material prior to its use in a patient. U.S. Pat. No. 5,897,573 describes how a low-level beta-emitting radioisotope may be incorporated into the chemical structure of suture material in order to inhibit an unwanted hyperplastic response. U.S. Pat. No. 5,897,573, filed Apr. 22, 1997, is hereby incorporated by reference as if fully set out herein.
Similarly, U.S. Pat. No. 6,042,600, filed Jan. 25, 1999, dealt with the problem of unwanted hyperplastic response in biological tissue by suggesting the irradiation of various medical devices before use in a patient. U.S. Pat. No. 6,042,600 was a continuation in part of U.S. Pat. No. 5,897,573. U.S. Pat. No. 6,042,600 describes how a low-level beta-emitting radioisotope may be incorporated into the chemical structure of a medical device. U.S. Pat. No. 6,042,600, filed Jan. 25, 1999, is hereby incorporated by reference as if fully set out herein.
Both of the two above-described patents generally prescribe chemically bonding the radioactive element to the structure of the medical device. However, there may be situations where it is not desirable to alter the chemical structure of the medical device to be used. Additionally, certain isotopes may not readily lend themselves to chemically attaching themselves to the molecules of the medical device.
Thus, there exists a need in the art for a radiation-emitting medical device where the radioactive element is not chemically bonded to the structure of the device. There also exists a need in the art for a method of making such medical devices. The invention described below remedies any shortcomings of the prior art.
Generally described, the present invention provides a radioactive medical device having beta radiation emitting capabilities for inhibiting an undesired hyperplastic response to the healing of biological tissue, and a method for making and using the devices. It is known that smooth muscle cell proliferation may be inhibited by varying degrees and types of radiation, particularly low level beta radiation. This knowledge is exploited by the radioactive medical devices and method described herein.
In a preferred embodiment, a method of creating a medical device that inhibits a hyperplastic response in biological tissue comprises the following steps: providing a first solvent in a container; introducing a salt or an acid of a radioactive isotope into the first solvent such that the salt or acid disassociates into ionic components so as to form a first solution; introducing a second solvent into the first solution so as to form a second solution; and introducing the medical device into the second solution, wherein the ionic components migrate from the second solution into the molecular structure of the medical device.
In a preferred embodiment, a medical device for inhibiting a hyperplastic response in biological tissue generally comprises polymeric hydrocarbon molecules forming the medical device and a salt or an acid of a radioactive isotope occluded within the polymeric hydrocarbon molecules. As a result of this structure, the radioactive isotope in the polymeric hydrocarbon molecules of the medical device inhibits a hyperplastic response in biological tissue.